Donor genetic variants as risk factors for thrombosis after liver transplantation: A genome-wide association study.
donors and donation
genetics
liver disease
liver transplantation/hepatology
microarray/gene array
thrombosis and thromboembolism
translational research/science
vascularized composite and reconstructive transplantation
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
30
12
2020
received:
05
08
2020
accepted:
04
01
2021
pubmed:
15
1
2021
medline:
18
9
2021
entrez:
14
1
2021
Statut:
ppublish
Résumé
Thrombosis after liver transplantation substantially impairs graft- and patient survival. Inevitably, heritable disorders of coagulation originating in the donor liver are transmitted by transplantation. We hypothesized that genetic variants in donor thrombophilia genes are associated with increased risk of posttransplant thrombosis. We genotyped 775 donors for adult recipients and 310 donors for pediatric recipients transplanted between 1993 and 2018. We determined the association between known donor thrombophilia gene variants and recipient posttransplant thrombosis. In addition, we performed a genome-wide association study (GWAS) and meta-analyzed 1085 liver transplantations. In our donor cohort, known thrombosis risk loci were not associated with posttransplant thrombosis, suggesting that it is unnecessary to exclude liver donors based on thrombosis-susceptible polymorphisms. By performing a meta-GWAS from children and adults, we identified 280 variants in 55 loci at suggestive genetic significance threshold. Downstream prioritization strategies identified biologically plausible candidate genes, among which were AK4 (rs11208611-T, p = 4.22 × 10
Identifiants
pubmed: 33445220
doi: 10.1111/ajt.16490
pmc: PMC8518362
pii: S1600-6135(22)08721-4
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3133-3147Informations de copyright
© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.
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